1. Field of the Invention
The present invention relates to an antidiabetic external skin application composition and, more specifically relates to an antidiabetic external skin application composition containing glibenclamide formulated therein.
2. Description of the Related Art
Glibenclamide is a sulfonylurea type oral hypoglycemic drug developed by cooperative study of Boehringer Mannheim and Hoechst in 1966 and is now commercially available in the field of drugs in the form of tablets (Trade name: Euglucon tablet available from Yamanouchi Seiyaku K. K., Japan, Trade name: Daonil available from Japan Hoechst). Such tablets containing, as an effective ingredient, glibenclamide formulated therein are conventionally used because they provide a strong hypoglycemic action at a small dosage, as described in, for example, Arzneim Forsch, vol. 19(8a), 1363-1368 (1969); Therapiewoche, vol. 18, 11-20 (1968).
Nevertheless, the tablet containing, as an effective ingredient, glibenclamide formulated therein is a powerful drug, as described in, for example, the attached statement of the powers of Euglucon tablet (Yamanouchi Seiyaku K. K.) that, since the tablet sometimes causes, as a side effect, a significant and prolonged hypoglycemia, the dosage regimen should be specially attentioned. Furthermore, since numbers of diabetes mellitus of aged people are recently increasing, as pointed out in, for example, Gekkan Yakuji (Japanese), Vol. 31, No. 4, 663-667 (1989), the dosage is especially important in the administration of the oral hypoglycemic drug to aged people.
In order to reduce the danger of the side effect as mentioned above, it is convenient that, if the tablet can be made in the form of a percutaneously absorbable external skin treatment agent (or ointment), the application amount can be easily adjusted and, in addition, even if rapid hypoglycemic action occurs, the agent can be easily washed out, for example, and therefore, the danger can be avoided. As the form of drug other than the oral administration type tablets, the application type external skin treatment agent (e.g., ointment) is known in the art (e.g., JP-A-4-18023, JP-A-3-86828). However, because of the characteristics of glibenclamide mentioned below, the prior application type external skin treatment agents have not been satisfied from the viewpoints of stability and percutaneous absorbability.
Namely, since glibenclamide is not soluble in most of solvents, it is very difficult to prepare the external skin treatment type agent thereof. Furthermore, although it is known in the art that glibenclamide is soluble in dimethylsulfoxide, it is not usable in the form of the dimethylsulfoxide solution from the viewpoint of safety. Thus, although the external skin, application type agent is desired, it has not been yet developed from the practical point of view.